Non-invasive Blood-brain Barrier Opening in Alzheimer's Disease Patients Using Focused Ultrasound

Inclusion Criteria: * 50 years of age or older. * Diagnosis of early Alzheimer's disease (AD) or mild cognitive impairment (MCI) at minimum. All following criteria must be met: * Probable MCI or AD consistent with criteria outlined in (McKhann et al 2011, Petersen et al 2018). * Mini Mental State Examination (MMSE) score between 12 and 26. * Modified Hachinski Ischemia Scale (MHIS) score of \<= 4 * Short form Geriatric Depression Scale (GDS) score of \<= 6. * PET scan confirming amyloid plaque load using Amyvid (18F-Florbetapir). * Ability to provide informed consent. Exclusion Criteria: * Contraindication for Magnetic Resonance Imaging (MRI). * Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity). * Prior brain surgery, including deep brain stimulation. * Metallic implants. * Moderate or severe uncontrolled hypertension (systolic blood pressure \> 140 mmHg). * Abnormal coagulation profile, e.g. hemophilia A or B. * Coagulopathy or under anticoagulant therapy. * History of stroke or cardiovascular disease. * Active/detectable gingivitis, herpes simplex, hepatitis, tuberculosis, and minor skin or respiratory infections. * History of seizure disorder. * History of asthma or allergies to food or medication with significant symptoms in past 3 years. * Severe brain atrophy. * Inability to comply with the procedures of the protocol, including follow-up MRI scans. * Pregnancy or lactation. * Impaired renal function with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 provided by a standard blood test at maximum 2 weeks prior to the ultrasound treatment. * Active infection/inflammation. * Acute or chronic hemorrhages, i.e. \> 4 lobar microbleeds, and no siderosis or macrohemorrhages. * Tumors or space occupying lesions. * Meningeal enhancements. * Intracranial hypotension.